Bacillus thuringiensis (Bt) pore-forming crystal proteins (Cry) are toxic towards insects and nematodes. The nematode C. elegans provides an excellent model to study the mechanism of Cry protein toxicity. In addition, C. elegans can be used to determine how a host defends itself against a pore-forming bacterial toxin. One aim of this proposal is to use a previously isolated C. elegans mutant that is hypersensitive to the Bt toxin Cry5B to understand host factors that influence toxicity and form part of an innate immune response. The mutant allele from this Cry5B hypersensitive C. elegans strain will be identified, and the function of the encoded protein studied to determine its response to toxin. An additional aim will be to isolate more Cry5B hypersensitive mutants via genetic screens to identify other host components that affect the response to a pore-forming toxin. Many human bacterial pathogens use pore-forming toxins as components of their pathogenic arsenal. Understanding cellular responses to this class of toxins will lead to a better understanding of how they cause disease and how host factors can influence toxicity.